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Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.

Background: Macrophage migration inhibitory factor (MIF) was one of the first lymphokine activities to be discovered and was described almost 30 years ago to be a soluble factor(s) produced by activated T lymphocytes. In more recent studies, MIF has been "rediscovered" to be an abundant, pre-formed constituent of the anterior pituitary gland and the macrophage, and to be a critical component in the host response to septic shock. Pituitary-derived MIF enters the circulation after infectious or stressful stimuli and appears to act to counterregulate glucocorticoid suppression of cytokine production. Materials and Methods: Immunoelectron microscopy utilizing a combination of anti-MIF and anti-pituitary hormone-specific antibodies was used to study the ultrastructural localization of MIF within the anterior pituitary gland. Pituitaries were obtained from resting, unstimulated mice and from mice 16 hr after endotoxin administration. The release of MIF also was investigated in vitro by examining the effect of corticotropin-releasing hormone (CRH) on the AtT-20, corticotrophic cell line.Results: MIF localizes to granules present exclusively in ACTH and TSH secreting cells. Within each cell type, a subset of granules was found to contain both MIF and ACTH, or MIF and TSH. The pituitary content of MIFcontaining granules decreased significantly after experimentally induced endotoxemia. In seven pituitaries examined 16 hr after LPS injection, the number of MIFpositive granules diminished by 38% in corticotrophic cells and by 48% in thyrotrophic cells when compared with controls (p < 0.05). CRH was observed to be a potent MIF secretagogue in vitro, inducing the release of MIF from corticotrophic cells at concentrations lower than that required for ACTH release. Conclusion: These data provide ultrastructural information that identify MIF to be a novel anterior pituitary hormone, support earlier studies showing a time-dependent release of pituitary MIWF during endotoxemia, and suggest an important, systemic role for MIF in the stress response to infection and other stimuli. years, however, the specific biological functions of MIF were unknown, and an appreciation of the important physiological role of this protein has emerged only recently. For instance, significant quantities of pre-formed MIF protein have been identified to be present in the anterior pituitary gland and in monocytes/macrophages and to be released into the bloodstream in response to invasive stimuli (3,4). MIF plays a pivotal role in the host response to endotoxic shock, 781 782

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